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The –700/–310 Fragment of the Apolipoprotein A-IV Gene Combined with the –890/–500 Apolipoprotein C-III Enhancer Is Sufficient to Direct a Pattern of Gene Expression Similar to That for the Endogenous Apolipoprotein A-IV Gene*

J. Le Beyec,V. Chauffeton,Horng-Yuan Kan,Pierre-Luc Janvier,C. Cywiner‐Golenzer,F. Châtelet,A. Kalopissis,V. Zannis,J. Chambaz,M. Pinçon-Raymond,P. Cardot

Published 1999 in Journal of Biological Chemistry

ABSTRACT

Spatial gene expression in the intestine is mediated by specific regulatory sequences. The three genes of the apoA-I/C-III/A-IV cluster are expressed in the intestine following cephalocaudal and crypt-to-villus axes. Previous studies have shown that the –780/–520 enhancer region of the apoC-III gene directs the expression of the apoA-I gene in both small intestinal villi and crypts, implying that other unidentified elements are necessary for a normal intestinal pattern of apoA-I gene expression. In this study, we have characterized transgenic mice expressing the chloramphenicol acetyltransferase gene under the control of different regions of the apoC-III and apoA-IV promoters. We found that the –890/+24 apoC-III promoter directed the expression of the reporter gene in crypts and villi and did not follow a cephalocaudal gradient of expression. In contrast, the −700/+10 apoA-IV promoter linked to the −500/−890 apoC-III enhancer directed the expression of the reporter gene in enterocytes with a pattern of expression similar to that of the endogenous apoA-IV gene. Furthermore, linkage of the −700/−310 apoA-IV distal promoter region to the −890/+24 apoC-III promoter was sufficient to restore the appropriate pattern of intestinal expression of the reporter gene. These findings demonstrate that the −700/−310 distal region of the apoA-IV promoter contains regulatory elements that, in combination with proximal promoter elements and the −500/−890 enhancer, are necessary and sufficient to restrict apoC-III and apoA-IV gene expression to villus enterocytes of the small intestine along the cephalocaudal axis.

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